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To date, although several studies have investigated the circulating levels of brain-derived neurotrophic factor (BDNF) in children with autism spectrum disorder (ASD), only a few authors have addressed their evaluation in adults. Furthermore, an important limitation of these studies lies in the fact that circulating BDNF is stored in platelets and released into the circulation when needed. To the best of our knowledge, a very limited number of studies have related peripheral BDNF values to platelet counts, and yet no study has evaluated intra-platelet BDNF levels in adults with ASD. In this framework, the aim of the present work is to pave the way in this field and evaluate platelet BNDF levels in adult ASD patients, as well as their correlation with autistic symptoms and related psychopathological dimensions. We recruited 22 ASD and 22 healthy controls, evaluated with the Adult autism subthreshold spectrum (AdAS Spectrum), the Social Anxiety Spectrum-self report (SHY-SR), the Trauma and loss spectrum-self report (TALS-SR), the Work and Social Adjustment Scale (WSAS), and the Mood Spectrum-self report for suicidality. Intra-platelet BDNF levels were also assessed. The results highlighted lower BDNF levels in the ASD group; moreover, AdAS Spectrum and WSAS total score as well as AdAS Spectrum Restricted interest and rumination, WSAS Private leisure activities, TALS-SR Arousal, and SHY-SR Childhood domains were significant negative predictors of platelet BDNF levels.
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Honeybees (Apis mellifera L.) have to face many challenges, including Varroa destructor infestation, associated with viral transmission. Oxalic acid is one of the most common treatments against Varroa. Little is known about the physiological effects of oxalic acid, especially those on honeybees' immune systems. In this study, the short-term effects (0-96 h) of oxalic acid treatment on the immune system components (i.e., glucose oxidase, phenoloxidase, glutathione S-transferase, catalase activities, and vitellogenin contents) of house bees were preliminarily investigated. Oxalic acid contents of bee bodies and haemolymphs were also measured. The results confirm that oxalic acid is constitutively present in bee haemolymphs and its concentration is not affected by treatment. At 6 h after the treatment, a maximum peak of oxalic acid content was detected on bees' bodies, which gradually decreased after that until physiological levels were reached at 48 h. In the immune system, the oxalic acid treatment determined a peak in glucose oxidase activity at 48 h, indicating a potential defence response and an increase in vitellogenin content at 24 h. No significant changes were recorded in phenoloxidase, glutathione S-transferase, and catalase activities. These results suggest a time-dependent response to oxalic acid, with potential immune system activation in treated bees.
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Post-traumatic stress disorder (PTSD) is a highly disabling mental disorder arising after traumatism exposure, often revealing critical and complex courses when comorbidity with bipolar disorder (BD) occurs. To search for PTSD or depression biomarkers that would help clinicians define BD presentations, this study aimed at preliminarily evaluating circulating brain-derived-neurotrophic factor (BDNF) levels in BD subjects with PTSD or experiencing a major depressive episode versus controls. Two bloodstream BDNF components were specifically investigated, the storage (intraplatelet) and the released (plasma) ones, both as adaptogenic/repair signals during neuroendocrine stress response dynamics. Bipolar patients with PTSD (n = 20) or in a major depressive episode (n = 20) were rigorously recruited together with unrelated healthy controls (n = 24) and subsequently examined by psychiatric questionnaires and blood samplings. Platelet-poor plasma (PPP) and intraplatelet (PLT) BDNF were measured by ELISA assays. The results showed markedly higher intraplatelet vs. plasma BDNF, confirming platelets' role in neurotrophin transport/storage. No between-group PPP-BDNF difference was reported, whereas PLT-BDNF was significantly reduced in depressed BD patients. PLT-BDNF negatively correlated with mood scores but not with PTSD items like PPP-BDNF, which instead displayed opposite correlation trends with depression and manic severity. Present findings highlight PLT-BDNF as more reliable at detecting depression than PTSD in BD, encouraging further study into BDNF variability contextually with immune-inflammatory parameters in wider cohorts of differentially symptomatic bipolar patients.
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Trastorno Bipolar , Trastorno Depresivo Mayor , Trastornos por Estrés Postraumático , Humanos , Biomarcadores , Factor Neurotrófico Derivado del EncéfaloRESUMEN
Searching for artificial diets positively affecting the survival, immune and antioxidant systems of honey bees is one of main challenges occurring in beekeeping. Among nutrients, lipids play a significant role in insect nutrition as structural components in cell membranes, energy sources and reserves, and are involved in many physiological processes. In this context, the aim of this work was to investigate the effect of 0.5% and 1% coconut oil-enriched diet administration on newly emerged and forager bees survival rate, feed intake, immune system, antioxidant system and both fat and vitellogenin content. In newly emerged bees, supplementation with 1% coconut oil determined a decrease in feed consumption, an increase in survival rate from the 3rd to 14th day of feeding, a short-term decrease in phenoloxidase activity, an increase in body fat and no differences in vitellogenin content. Conversely, supplementation with 0.5% coconut oil determined an increase in survival rate from the 3rd to 15th day of feeding and an increase in fat content in the long term (i.e., 20 days). Regarding the forager bee diet, enrichment with 0.5% and 1% coconut oil only determined an increase in fat content. Therefore, supplementation with coconut oil in honey bee diets at low percentages (0.5 and 1%) determines fat gain. Further investigations to evaluate the use of such supplement foods to prevent the fat loss of weak families during winter are desirable.
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Converging, albeit scattered data mainly gathered in animals indicate that the neurotrophin brain-derived neurotrophic factor (BDNF) and the nonapeptide oxytocin (OT) interact in a cooperative way. Data in humans are really limited and indirect. Therefore, the aim of the present study was to explore the possible existence of a link between OT and BDNF in humans, by means of two peripheral markers, the platelet-poor-plasmatic-BDNF (PPP-BDNF) and the platelet BDNF (PLT-BDNF) and OT levels. Twenty-six young healthy controls of both sexes who volunteered for the study were included in the study. Fifty ml of peripheral venous blood were drawn from one-night fasting subjects between 8.00 and 9.00 a.m. The BDNF and OT assays were carried out according to common methods. Comparisons for continuous variables were performed by the Student's t-test for variables that follow a normal distribution, and by the Wilcoxon-Mann-Whitney test for variables not normally distributed. The correlations between biological markers were explored by calculating the Pearson's correlation coefficient or Spearman's rank correlation. The results showed that PLT-BDNF (pg/mg proteins, mean ± SD) and PPP-BDNF (pg/ml, mean ± SD) were 1546 ± 1844 and 10111 ± 1892, respectively. The OT levels (pg/ml, mean ± SD) were 13.92 ± 4.54. The OT levels were significantly higher in women than in men. The Spearman's analysis revealed a statistically significant and negative correlation between OT levels and PLT-BDNF (R = -0.543, p = 0.004). The findings of this study highlight the presence of a significant and negative correlation between OT and PLT-BDNF in a small group of healthy controls of both sexes. In any case, despite all the limits of peripheral biomarkers, they suggest that this reciprocal influence might have a downstream homeostatic function dampening one activity when the other is activated or no longer necessary, maybe at the level of the stress and/or immune systems.
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This study seeks to offer a contribution to the method of subtyping major depressed patients by exploring the possible relationships between circulating brain-derived neurotrophic factor (BDNF), different peripheral inflammatory/metabolic markers in the blood and clinical characteristics. Thirty-nine patients, thoroughly diagnosed according to the DSM-5 criteria, underwent a comprehensive set of evaluations encompassing structured interviews, rating scales and a panel of blood tests. Correlation and comparison analyses were carried out by means of non-parametric statistical tests. Concurrently, a principal component analysis was performed to explain biochemical variance. The findings of our research unveiled that leukocyte counts, their ratios and other inflammatory parameters are positively correlated with depression scores. Moreover, we found variations within the BDNF pools of depressed patients. Specifically, higher levels of platelet-poor plasma BDNF (PPP-BDNF) were correlated with augmented inflammatory markers in patients showing specific episode characteristics, whereas reduced platelet BDNF (PLT-BDNF) provided a better indication of the changes that were linked to a diagnosis of long-term depression. Our findings suggest that PPP-BDNF and PLT-BDNF might differentiate depression conditions. They also imply usefulness in appraising peripheral biomarker profiles in patients for a deeper characterization of major depressive episodes. At the same time, it is plausible that they might constitute novel avenues for developing more tailored therapeutic strategies for patients with MDs.
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Involving 1 million people a year, suicide represents one of the major topics of psychiatric research. Despite the focus in recent years on neurobiological underpinnings, understanding and predicting suicide remains a challenge. Many sociodemographical risk factors and prognostic markers have been proposed but they have poor predictive accuracy. Biomarkers can provide essential information acting as predictive indicators, providing proof of treatment response and proposing potential targets while offering more assurance than psychological measures. In this framework, the aim of this study is to open the way in this field and evaluate the correlation between blood levels of serotonin, brain derived neurotrophic factor, tryptophan and its metabolites, IL-6 and homocysteine levels and suicidality. Blood samples were taken from 24 adults with autism, their first-degree relatives, and 24 controls. Biochemical parameters were measured with enzyme-linked immunosorbent assays. Suicidality was measured through selected items of the MOODS-SR. Here we confirm the link between suicidality and autism and provide more evidence regarding the association of suicidality with increased homocysteine (0.278) and IL-6 (0.487) levels and decreased tryptophan (-0.132) and kynurenic acid (-0.253) ones. Our results suggest a possible transnosographic association between these biochemical parameters and increased suicide risk.
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Several heterogeneous pathophysiology pathways have been hypothesized for being involved in the onset and course of Post-Traumatic Stress Disorder (PTSD). This systematic review aims to summarize the current evidence on the role of inflammation and immunological dysregulations in PTSD, investigating possible peripheral biomarkers linked to the neuroimmune response to stress. A total of 44 studies on the dysregulated inflammatory and metabolic response in subjects with PTSD with respect to controls were included. Eligibility criteria included full-text publications in the English language, human adult samples, studies involving both subjects with a clinical diagnosis of PTSD and a healthy control group. The research was focused on specific blood neuroimmune biomarkers, namely IL-1ß, TNF-α, IL-6 and INF-γ, as well as on the potential harmful role of reduced antioxidant activity (involving catalase, superoxide dismutase and glutathione peroxidase). The possible role of the inflammatory-altered tryptophan metabolism was also explored. The results showed conflicting data on the role of pro-inflammatory cytokines in individuals with PTSD, and a lack of study regarding the other mediators investigated. The present research suggests the need for further studies in human samples to clarify the role of inflammation in the pathogenesis of PTSD, to define potential peripheral biomarkers.
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Trastornos por Estrés Postraumático , Adulto , Humanos , Trastornos por Estrés Postraumático/diagnóstico , Citocinas , Factor de Necrosis Tumoral alfa , Inflamación , BiomarcadoresRESUMEN
BACKGROUND: The importance of recognizing different kinds of autism spectrum presentations among adults, including subthreshold forms and the broad autism phenotype (BAP), has been increasingly highlighted in recent studies. Meanwhile, the possible involvement of immune system deregulation and altered methylation/trans-sulfuration processes in autism spectrum disorder (ASD) is gaining growing attention, but studies in this field are mainly focused on children. In this framework, the aim of this study was to compare plasmatic concentrations of IL-6 and homocysteine (HCY) among adults with ASD, their first-degree relatives, and healthy controls (CTLs), investigating also possible correlations with specific autism symptoms. METHODS: Plasma concentrations of IL-6 and HCY were measured in a group of adult subjects with ASD, their first-degree relatives (BAP group), and healthy controls (CTL). All participants were also evaluated with psychometric instruments. RESULTS: IL-6 and HCY concentrations were significantly higher in the ASD group than in CTLs, while BAP subjects reported intermediate results. Significant correlations were reported between biochemical parameters and psychometric scales, particularly for the dimension of ruminative thinking. CONCLUSIONS: These findings support the hypothesis of a key involvement of HCY-related metabolism and immune system alteration in autism spectrum pathophysiology. HCY and IL-6 seem to show different associations with specific autism dimensions.
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BACKGROUND: Increasing literature highlighted alterations of tryptophan (TRP) metabolism and kynurenine (KYN) pathway in children with autism spectrum disorder (ASD). However, no study specifically focused on adult samples. Meanwhile, several authors stressed the relevance of investigating neurobiological correlates of adult forms of ASD and of those subthreshold ASD manifestations frequently found in relatives of ASD probands, known as broad autism phenotype (BAP). This work aimed to evaluate circulating levels of TRP and metabolites of KYN pathway in a sample of ASD adults, their first-degree relatives and controls (CTLs), investigating also the correlations between biochemical variables' levels and ASD symptoms. METHODS: A sample of ASD adults, together with a group of first-degree relatives (BAP group) and unrelated CTLs were assessed by means of psychometric scales. Circulating levels of TRP, KYN, quinolinic acid (QA), and kynurenic acid (KYNA) were assessed in all subjects. RESULTS: ASD patients reported significantly higher total scores than the other groups on all psychometric scales. BAP subjects scored significantly higher than CTLs. ASD patients reported significantly lower TRP levels than BAP and CTL groups. Moreover, significantly lower levels of KYNA were reported in both ASD and BAP groups than in CTLs. Specific patterns of associations were found between autism symptoms and biochemical variables. CONCLUSIONS: Our findings confirm in adult samples the presence of altered TRP metabolism through KYN pathway. The intermediate alterations reported among relatives of ASD patients further stress the presence of a continuum between subthreshold and full-threshold ASD phenotypes also from a biochemical perspective.
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Trastorno del Espectro Autista , Trastorno Autístico , Humanos , Quinurenina/metabolismo , Triptófano/metabolismo , Trastorno del Espectro Autista/diagnóstico , Ácido Quinurénico , FenotipoRESUMEN
Varroa destructor is a mite causing serious damage to western honey bees. Managed colonies require artificial varroa control, which may be best obtained by combining mechanical and chemical methods. This study explored the possible effects of the combination of queen caging and oxalic acid treatment on the immune system (glucose oxidase, phenoloxidase, and vitellogenin) and antioxidant enzymes (superoxide dismutase, catalase, and glutathione S transferase) of first post-treatment generation drones and workers (newly emerged, nurses, and foragers). The combination of queen caging and oxalic acid treatment caused a decrease in glucose oxidase activity only in drones. This could cause issues of cuticular sclerotization, making a drone prone to bite injuries, dehydration, and pathogens. No differences in phenoloxidase activity were recorded in both post-treatment drones and workers generation. Among worker bees, the treatment determined a lower vitellogenin content in newly emerged bees while the result was higher in nurse bees. However, the treatment did not significantly affect the antioxidant enzymes activity in either drones or workers. The results obtained in this investigation suggest that the combined anti-varroa treatments had no negative effects on oxidative stress in the first post-treatment generation bees, while effects did occur on the immune system. Further investigations on the potential effects of glucose oxidase decrease in drones and vitellogenin content variation in workers are desirable.
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Protein-supplemented artificial diets are widely used by beekeepers during winter and whenever food availability is low, yet no data are available concerning their effects on bees' health. In this work, the effects of two commercial diets enriched with 1.7% and 7.7% protein concentration on feed intake, survival rate, glucose oxidase, phenoloxidase and glutathione S-transferase in newly emerged and forager bees were tested. Administration of a 7.7% protein-enriched diet significantly reduced the lifespan of both newly emerged and forager bees, while only in foragers a significantly higher feed intake was recorded. In newly emerged bees, administration of a high-protein-enriched diet stimulated glucose oxidase production at the 10th day of feeding, determined a reduction of phenoloxidase and did not affect glutathione S-transferase activity. In forager bees, a high level of protein inclusion did not determine any significant variation in either glucose oxidase, phenoloxidase or glutathione S-transferase activity. Therefore, the results obtained in this investigation suggest that administration of commercial protein diets negatively affect honey bee health, determining an increase in mortality. Further investigations on the effect of concentration and quality of proteins are desirable to provide beekeepers with scientific evidence on protein feeding.
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Royal Jelly is a nutrient secretion of nurse bees and a high interest functional food in human nutrition. Very little information is available on its chemical composition integrity and enzymatic activity during shelf life and assessment of new freshness markers are desirable for its conservation. In this study, the activity of glucose oxidase, five proteases and two antioxidant enzymes in refrigerated and frozen Royal Jelly for different storage times was preliminary investigated. Refrigeration determined a significantly reduction in glucose oxidase and carboxypeptidase A-like activity in Royal Jelly after one year of storage while no differences were recorded in the activity of these enzymes in frozen samples. After one year of storage glucose oxidase and carboxypeptidase A-like activity resulted higher in frozen samples frozen than in refrigerate ones. Results obtained suggest that the activities of these enzymes may be good markers of Royal Jelly freshness within 1 year at refrigeration condition. Freezing could be a valid alternative storage method to ensure a higher preservation of glucose oxidase and carboxypeptidase A-like activities for at least 1 year. Further investigation to determine the timing of glucose oxidase inactivation/degradation under refrigerated conditions and the enzymatic activity trend under prolonged frozen conditions are desirable.
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OBJECTIVE: To provide evidence to the link between serotonin (5-HT), energy metabolism, and the human obese phenotype, the present study investigated the binding and function of the platelet 5-HT transporter (SERT), in relation to circulating insulin, leptin, and glycolipid metabolic parameters. METHODS: Seventy-four drug-free subjects were recruited on the basis of divergent body mass index (BMIs) (16.5-54.8 Kg/m2). All subjects were tested for their blood glycolipid profile together with platelet [3H]-paroxetine ([3H]-Par) binding and [3H]-5-HT reuptake measurements from April 1st to June 30th, 2019. RESULTS: The [3H]-Par Bmax (fmol/mg proteins) was progressively reduced with increasing BMIs (P < .001), without changes in affinity. Moreover, Bmax was negatively correlated with BMI, waist/hip circumferences (W/HC), triglycerides (TD), glucose, insulin, and leptin, while positively with high-density lipoprotein (HDL) cholesterol (P < .01). The reduction of 5-HT uptake rate (Vmax, pmol/min/109 platelets) among BMI groups was not statistically significant, but Vmax negatively correlated with leptin and uptake affinity values (P < .05). Besides, [3H]-Par affinity values positively correlated with glycemia and TD, while [3H]-5-HT reuptake affinity with glycemia only (P < .05). Finally, these correlations were specific of obese subjects, while, from multiple linear-regression analysis conducted on all subjects, insulin (P = .006) resulting negatively related to Bmax independently from BMI. CONCLUSIONS: Present findings suggest the presence of a possible alteration of insulin/5-HT/leptin axis in obesity, differentially impinging the density, function, and/or affinity of the platelet SERT, as a result of complex appetite/reward-related interactions between the brain, gut, pancreatic islets, and adipose tissue. Furthermore, they support the foremost cooperation of peptides and 5-HT in maintaining energy homeostasis.
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Leptina , Serotonina , Glucolípidos , Humanos , Insulina , Obesidad , TriglicéridosRESUMEN
Mammal's saliva contains a variety of electrolytes and proteins. They carry out an important role in the digestion process, in the antibacterial and antiviral activity, in lubrication and maintenance of oral general health status. It may also contain several enzymes according to dietary habits and general wellness. Sialochemistry is a valid alternative to the haematochemical analysis for the evaluation of animal health and nutritional status. At present, very little knowledge is available on health status and pathology of crested porcupine (Hystrix cristata) and no data are yet available on salivary enzymes. Between 2018 and 2020, a preliminary investigation of enzymatic activity on saliva samples was carried out from captured porcupines. In crested porcupine saliva, enzymatic activity of trypsin, chymotrypsin, N-Aminopeptidase, amylase, lignin peroxidise, cellulase and chitinase were recorded. Superoxide dismutase, catalase, glutathione S-transferase and alkaline phosphatase activity was also detected. The superoxide dismutase activity resulted higher (3.13 SD 3.58 U/mg proteins) than those of catalase (130.80 SD 110.65 mU/mg proteins) and glutathione S-transferase (20.21 SD 16.62 mM/mg proteins). Alkaline phosphatase activity resulted lower (5.91 SD 6.12 mU/mg proteins) than acidic phosphatase (19.00 SD 16.16 U/mg proteins) with the highest values of saliva alkaline phosphatases recorded in young individuals. These preliminary data bring new knowledge on crested porcupine saliva enzymes and may provide a useful tool for further investigation on the adaptive response of crested porcupine to different environmental condition and diet. Additional investigation concerning a possible alternative use of saliva enzymes as indicator of health and nutritional status of this rodent are desirable.
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Puercoespines , Animales , Conducta Alimentaria , Puercoespines/microbiología , Puercoespines/fisiología , SalivaRESUMEN
ß-glucans can activate the animal innate immune system by acting as immune-modulators and inducing various stimulatory effects. The aim of this study was to investigate the effect of 1,3-1,6 ß-glucans administered orally for 96 h on Apis mellifera workers (newly emerged and nurse bees). ß-glucans were included in honey and syrup. Survival rate and phenoloxidase activity were measured. In both newly emerged and nurse bees, ß-glucans supplementation did not affect survival rate (p > 0.05). Conversely, phenoloxidase activity was higher in both newly emerged bees (p = 0.048) and nurse bees (p = 0.014) fed with a honey diet enriched with ß-glucans compared to those fed with only honey. In both the newly emerged and nurse bees, no statistical differences in phenoloxidase activity were recorded between the group fed with a syrup-based diet enriched with ß-glucans and the control group (p > 0.05). The absence of significant variation in survival suggests that the potential negative effect of ß-glucans in healthy bees could be mitigated by their metabolism. Conversely, the inclusion of ß-glucans in a honey-based diet determined an increase of phenoloxidase activity, suggesting that the effect of ß-glucan inclusion in the diet of healthy bees on phenoloxidase activity could be linked to the type of base-diet. Further investigations on ß-glucans metabolism in bees, on molecular mechanism of phenoloxidase activation by 1,3-1,6 ß-glucans, and relative thresholds are desirable. Moreover, investigation on the combined action of honey and ß-glucans on phenoloxidase activity are needed.
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OBJECTIVES: Physicians' gestalt is central in the diagnostic pipeline of suspected COVID-19, due to the absence of a single tool allowing conclusive rule in or rule out. The aim of this study was to estimate the diagnostic test characteristics of physician's gestalt for COVID-19 in the emergency department (ED), based on clinical findings or on a combination of clinical findings and bedside imaging results. METHODS: From April 1 to April 30, 2020, patients with suspected COVID-19 were prospectively enrolled in two EDs. Physicians prospectively dichotomized patients in COVID-19 likely or unlikely twice: after medical evaluation of clinical features (clinical gestalt [CG]) and after evaluation of clinical features and results of lung ultrasound or chest x-ray (clinical and bedside imaging-integrated gestalt [CBIIG]). The final diagnosis was adjudicated after independent review of 30-day follow-up data. RESULTS: Among 838 ED enrolled patients, 193 (23%) were finally diagnosed with COVID-19. The area under the curve (AUC), sensitivity, and specificity of CG and CBIIG for COVID-19 were 80.8% and 91.6% (p < 0.01), 82.9% and 91.4% (p = 0.01), and 78.6% and 91.8% (p < 0.01), respectively. CBIIG had similar AUC and sensitivity to reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 on the first nasopharyngeal swab per se (93.5%, p = 0.24; and 87%, p = 0.17, respectively). CBIIG plus RT-PCR had a sensitivity of 98.4% for COVID-19 (p < 0.01 vs. RT-PCR alone) compared to 95.9% for CG plus RT-PCR (p = 0.05). CONCLUSIONS: In suspected COVID-19, CG and CBIIG have fair diagnostic accuracy, in line with physicians' gestalt for other acute conditions. Negative RT-PCR plus low probability based on CBIIG can rule out COVID-19 with a relatively low number of false-negative cases.
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COVID-19 , Infecciones por Coronavirus , Médicos , Humanos , Estudios Prospectivos , SARS-CoV-2 , Sensibilidad y EspecificidadRESUMEN
Threats, challenging events, adverse experiences, predictable or unpredictable, namely stressors, characterize life, being unavoidable for humans. The hypothalamus-pituitary-adrenal axis (HPA) and the sympathetic nervous system (SNS) are well-known to underlie adaptation to psychosocial stress in the context of other interacting systems, signals and mediators. However, much more effort is necessary to elucidate these modulatory cues for a better understanding of how and why the "brain-body axis" acts for resilience or, on the contrary, cannot cope with stress from a biochemical and biological point of view. Indeed, failure to adapt increases the risk of developing and/or relapsing mental illnesses such as burnout, post-traumatic stress disorder (PTSD), and at least some types of depression, even favoring/worsening neurodegenerative and somatic comorbidities, especially in the elderly. We will review here the current knowledge on this area, focusing on works presenting the main brain centers responsible for stressor interpretation and processing, together with those underscoring the physiology/biochemistry of endogenous stress responses. Autonomic and HPA patterns, inflammatory cascades and energy/redox metabolic arrays will be presented as allostasis promoters, leading towards adaptation to psychosocial stress and homeostasis, but also as possible vulnerability factors for allostatic overload and non-adaptive reactions. Besides, the existence of allostasis buffering systems will be treated. Finally, we will suggest promising lines of future research, particularly the use of animal and cell culture models together with human studies by means of high-throughput multi-omics technologies, which could entangle the biochemical signature of resilience or stress-related illness, a considerably helpful facet for improving patients' treatment and monitoring.
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Alostasis , Mediadores de Inflamación , Anciano , Animales , Encéfalo , Homeostasis , Humanos , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Estrés PsicológicoRESUMEN
BACKGROUND: While both depression and aging have been associated with oxidative stress and impaired immune response, little is known about redox patterns in elderly depressed subjects. This study investigates the relationship between redox/inflammatory patterns and depression in a sample of elderly adults. METHODS: The plasma levels of the advanced products of protein oxidation (AOPP), catalase (CAT), ferric reducing antioxidant power (FRAP), glutathione transferase (GST), interleukin 6 (IL-6), superoxide dismutase (SOD), total thiols (TT), and uric acid (UA) were evaluated in 30 patients with mood disorders with a current depressive episode (depressed patients, DP) as well as in 30 healthy controls (HC) aged 65 years and over. Subjects were assessed with the Hamilton Depression Rating Scale (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Geriatric Depression Rating Scale (GDS), the Scale for Suicide Ideation (SSI), the Reason for Living Inventory (RFL), the Activities of Daily Living (ADL), and the Instrumental Activity of Daily Living (IADL). RESULTS: DP showed higher levels than HC of AOPP and IL-6, while displaying lower levels of FRAP, TT, and CAT. In the DP group, specific correlations were found among biochemical parameters. SOD, FRAP, UA, and TT levels were also significantly related to psychometric scale scores. CONCLUSION: Specific alterations of redox systems are detectable among elderly DP.
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Catalasa/sangre , Trastorno Depresivo Mayor/sangre , Glutatión Transferasa/sangre , Interleucina-6/sangre , Superóxido Dismutasa/sangre , Actividades Cotidianas/psicología , Anciano , Anciano de 80 o más Años , Trastorno Depresivo Mayor/psicología , Femenino , Humanos , Inflamación/sangre , Masculino , Oxidación-Reducción , Escalas de Valoración Psiquiátrica , Ideación SuicidaRESUMEN
The most commonly used antidepressant drugs are the serotonin transporter inhibitors. Their effects depend strongly on the selectivity for a single monoamine transporter compared to other amine transporters or receptors, and the selectivity is roughly influenced by the spatial protein structure. Here, we provide a computational study on three human monoamine transporters, i.e., DAT, NET, and SERT. Starting from the construction of hDAT and hNET models, whose three-dimensional structure is unknown, and the prediction of the binding pose for 19 known inhibitors, 3D-QSAR models of three human transporters were built. The training set variability, which was high in structure and activity profile, was validated using a set of in-house compounds. Results concern more than one aspect. First of all, hDAT and hNET three-dimensional structures were built, validated, and compared to the hSERT one; second, the computational study highlighted the differences in binding site arrangement statistically correlated to inhibitor selectivity; third, the profiling of new inhibitors pointed out a conservation of the inhibitory activity trend between rabbit and human SERT with a difference of about 1 order of magnitude; fourth, binding and functional studies confirmed 4-(benzyloxy)-4-phenylpiperidine 20a-d and 21a-d as potent SERT inhibitors. In particular, one of the compounds (compound 20b) revealed a higher affinity for SERT than paroxetine in human platelets.